The goal is to identify and map cancer susceptibility genes in man. Studies are currently in progress on 21 cancer families with pedigrees containing 11 to 425 individuals (all but one contain 50 or fewer members). The number of individuals with a primary cancer type varies from 3 to 21. A cancer-free pedigree containing 50 members is also under investigation. Typing of HLA and red blood cell and serum markers has been completed for 12 of these families. Many more extended pedigrees are anticipated to be included in this study. A wide variety of biochemical and DNA markers are under investigation in the search for cancer susceptibility genes. Specifically, the following studies will be included: (1)\performance of linkage studies on high-risk cancer pedigrees using "non-familial" polymorphic oncogene probes as genetic markers; (2)\isolation and characterization of the genetic segregation of "familial" polymorphic transforming genes; (3)\expansion of the mapping of chromosome 6p by characterizing new markers for DNA regions adjacent to the MHC; (4)\application of new MHC-linked markers to expand linkage analyses of cancer pedigrees with previously suggested HLA linkage to CSG's; and (5)\identification of new high-risk cancer families.